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Updated: Jul 12, 2026
Induction of Experimental Autoimmune Encephalomyelitis in Mice and Evaluation of the Disease-dependent Distribution of Immune Cells in Various Tissues
Published on: May 8, 2016
Differential virus replication, cytokine production, and antigen-presenting function by microglia from susceptible
Young-Hee Jin1, Mani Mohindru, Min H Kang
1Department of Microbiology and Immunology, Northwestern University Feinberg Medical School, 303 E. Chicago Avenue, Chicago, IL 60611, USA.
Abstract:
Infection with Theiler's murine encephalomyelitis virus (TMEV) in the central nervous system (CNS) causes an immune system-mediated demyelinating disease similar to human multiple sclerosis in susceptible but not resistant strains of mice. To understand the underlying mechanisms of differential susceptibility, we analyzed viral replication, cytokine production, and costimulatory molecule expression levels in microglia and macrophages in the CNS of virus-infected resistant C57BL/6 (B6) and susceptible SJL/J (SJL) mice. Our results indicated that message levels of TMEV, tumor necrosis factor alpha, beta interferon, and interleukin-6 were consistently higher in microglia from virus-infected SJL mice than in those from B6 mice. However, the levels of costimulatory molecule expression, as well as the ability to stimulate allogeneic T cells, were significantly lower in TMEV-infected SJL mice than in B6 mice. In addition, microglia from uninfected naïve mice displayed differential viral replication, T-cell stimulation, and cytokine production, similar to those of microglia from infected mice. These results strongly suggest that different levels of intrinsic susceptibility to TMEV infection, cytokine production, and T-cell activation ability by microglia contribute to the levels of viral persistence and antiviral T-cell responses in the CNS, which are critical for the differential susceptibility to TMEV-induced demyelinating disease between SJL and B6 mice.
Insights
Microglia exhibit intrinsic differences in susceptibility to Theiler's murine encephalomyelitis virus (TMEV) infection, impacting cytokine production and T-cell activation. These variations influence viral persistence and immune responses, explaining differential susceptibility to TMEV-induced demyelination.
Area of Science:
- Neuroimmunology
- Virology
- Immunology
Background:
- Theiler's murine encephalomyelitis virus (TMEV) infection in the central nervous system (CNS) causes demyelinating disease.
- Susceptibility to TMEV-induced disease varies between mouse strains, resembling human multiple sclerosis.
- Understanding differential susceptibility mechanisms is crucial for neuroinflammatory disease research.
Purpose of the Study:
- To investigate the mechanisms behind differential susceptibility to TMEV-induced demyelinating disease.
- To compare viral replication, cytokine production, and costimulatory molecule expression in microglia and macrophages from resistant and susceptible mice.
- To elucidate the role of microglia in TMEV pathogenesis and differential disease outcomes.
Main Methods:
- Analysis of viral replication in microglia and macrophages from C57BL/6 (resistant) and SJL/J (susceptible) mice.
- Quantification of cytokine (TNF-α, IFN-β, IL-6) message levels in CNS microglia.
- Assessment of costimulatory molecule expression and allogeneic T-cell stimulation by microglia.
Main Results:
- Higher TMEV replication and pro-inflammatory cytokine message levels (TNF-α, IFN-β, IL-6) were observed in microglia from susceptible SJL mice compared to resistant B6 mice.
- Susceptible SJL microglia exhibited lower costimulatory molecule expression and reduced ability to stimulate T cells.
- Naïve microglia from both strains showed intrinsic differences in viral replication, cytokine production, and T-cell activation potential.
Conclusions:
- Intrinsic differences in microglia's susceptibility to TMEV, cytokine production, and T-cell activation ability contribute to differential disease outcomes.
- These microglial characteristics influence viral persistence and antiviral T-cell responses in the CNS.
- Microglial intrinsic properties are critical factors in determining susceptibility to TMEV-induced demyelinating disease.
